One-pot synthesis of group 8 transition metal carbene complexes useful as olefin metathesis catalysts

ABSTRACT

The invention provides a novel method for synthesizing transition metal carbene complexes useful as olefin metathesis catalysts. The method is a convenient one-pot synthesis in which transition metal carbenes are prepared in high yield from readily available starting materials via a dihydrogen complex containing two different anionic ligands, preferably a phosphine and a heteroatom-stabilized carbene. The invention additionally provides a method for synthesizing precursors to carbene ligands useful, inter alia, in the aforementioned one-pot synthesis. The precursors are in the form of trichloromethyl adducts of the formula L 1 -CCl 3 , where L 1  is a heteroatom-stabilized carbene ligand, and are prepared by contacting an unsaturated, ionized analog of L-CCl 3  with a non-nucleophilic base in the presence of chloroform.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority under 35 U.S.C. §119(e)(1) tothe following provisional U.S. patent applications: Ser. No. 60/281,046,filed Apr. 2, 2001; and Ser. No. 60/309,806, filed Aug. 1, 2001. Thedisclosures of the aforementioned applications are incorporated byreference in their entireties.

ACKNOWLEDGEMENT OF GOVERNMENT SUPPORT

[0002] This invention was developed with U.S. Government support undergrant numbers 2 R01 GM31332 and 3 RO1 GM31332-16 awarded by the NationalInstitutes of Health, and under grant number CHE 9809856 awarded by theNational Science Foundation. The Government has certain rights in theinvention.

TECHNICAL FIELD

[0003] This invention relates generally to a method for synthesizingGroup 8 transition metal carbene complexes useful as olefin metathesiscatalysts, and more particularly relates to a novel one-pot synthesis ofmixed ligand transition metal carbene catalysts that contain aheteroatom-stabilized carbene ligand, e.g., an imidazolylidene ligand.The invention also pertains to a method for synthesizing a precursor toheteroatom-stabilized carbene ligands, particularly1,3-disubstituted-2-trichloromethyl-5-dihydroimidazolidene.

BACKGROUND OF THE INVENTION

[0004] To the synthetic organic or polymer chemist, simple methods forforming carbon—carbon bonds are extremely important and valuable tools.One method of C—C bond formation that has proved particularly useful istransition-metal catalyzed olefin metathesis. “Olefin metathesis,” as isunderstood in the art, refers to the metal-catalyzed redistribution ofcarbon—carbon bonds. See Trnka and Grubbs (2001) Acc. Chem. Res.34:18-29. Over two decades of intensive research effort has culminatedin the discovery of well-defined ruthenium and osmium carbenes that arehighly active olefin metathesis catalysts and stable in the presence ofa variety of functional groups.

[0005] These ruthenium and osmium carbene complexes have been describedin U.S. Pat. Nos. 5,312,940, 5,342,909, 5,831,108, 5,969,170, 6,111,121,and 6,211,391 to Grubbs et al., assigned to the California Institute ofTechnology. The ruthenium and osmium carbene complexes disclosed inthese patents all possess metal centers that are formally in the +2oxidation state, have an electron count of 16, and arepenta-coordinated. These catalysts are of the general formula (I)

[0006] where M is a Group 8 transition metal such as ruthenium orosmium, X and X′ are anionic ligands, L and L′ are neutral electrondonors, and R and R′ are specific substituents, e.g., one may be H andthe other may be a substituted or unsubstituted hydrocarbyl group suchas phenyl or C═C(CH₃)₂. Such complexes have been disclosed as useful incatalyzing a variety of olefin metathesis reactions, including ringopening metathesis polymerization (“ROMP”), ring closing metathesis(“RCM”), acyclic diene metathesis polymerization (“ADMET”), ring-openingmetathesis (“ROM”), and cross-metathesis (“CM” or “XMET”) reactions.

[0007] For the most part, such metathesis catalysts have been preparedwith phosphine ligands, e.g., triphenylphosphine ordimethylphenylphospine, exemplified by the well-defined,metathesis-active ruthenium alkylidene complexes (II) and (III)

[0008] wherein “Cy” is a cycloalkyl group such as cyclohexyl orcyclopentyl. See U.S. Pat. No. 5,917,071 to Grubbs et al. and Trnka andGrubbs, cited supra. These compounds are highly reactive catalystsuseful for catalyzing a variety of olefin metathesis reactions, and aretolerant of many different functional groups. However, as has beenrecognized by those in the field, the compounds display low thermalstability, decomposing at relatively low temperatures. Jafarpour andNolan (2000) Organometallics 19(11):2055-2057.

[0009] Recently, however, significant interest has focused on the use ofN-heterocyclic carbene ligands as superior alternatives to phosphines.See, e.g., Trnka and Grubbs, supra; Bourissou et al. (2000) Chem. Rev.100:39-91; Scholl et al. (1999) Tetraheron Lett. 40:2247-2250; Scholl etal. (1999) Organic Lett. 1(6):953-956; and Huang et al. (1999) J. Am.Chem. Soc. 121:2674-2678. N-heterocyclic carbene ligands offer manyadvantages, including readily tunable steric bulk, vastly increasedelectron donor character, and compatibility with a variety of metalspecies. In addition, replacement of one of the phosphine ligands inthese complexes significantly improves thermal stability. The vastmajority of research on these carbene ligands has focused on theirgeneration and isolation, a feat finally accomplished by Arduengo andcoworkers within the last ten years (see, e.g., Arduengo et al. (1999)Acc. Chem. Res. 32:913-921). Representative of these second generationcatalysts are the four ruthenium complexes (IVA), (IVB), (VA) and (VB):

[0010] In the above structures, Cy is as defined previously, “IMes”represents 1,3-dimesityl-imidazol-2-ylidene IMes:

[0011] and “IMesH₂” represents1,3-dimesityl-4,5-dihydroimidazol-2-ylidene IMesH₂:

[0012] These transition metal carbene complexes, particularly thosecontaining a ligand having the 4,5-dihydroimidazol-2-ylidene structure,such as in IMesH₂, have been found to address a number of previouslyunsolved problems in olefin metathesis reactions, particularlycross-metathesis reactions. These problems span a variety of reactionsand starting materials.

[0013] Previously, synthetic routes to such complexes have involvedmultiple steps and have required air- and moisture-sensitive carbeneprecursors as starting materials. Such methods are described, forexample, by Scholl et al. (1999) Tet. Lett. 40:2247-2250, Kingsbury etal. (1999) J. Am. Chem. Soc. 121:791-799, and Huang et al. (1999), citedsupra. There is, accordingly, a need in the art for a practical,convenient synthesis of catalysts such as (IVA), (IVB), (V), and (VB),possessing an N-heterocyclic carbene ligand, which provides the desiredcomplexes in high yield using air- and moisture-stable precursors. Itwould also be desirable if such a synthesis were broadly applicable inthe manufacture of other mixed ligand metal alkylidenes as well asrelated complexes, e.g., mixed ligand metal vinylidenes. The presentinvention is, in part, directed to such a synthesis.

[0014] The invention additionally addresses the problems those workingin the field have encountered with synthesis of N-heterocyclic carbenereactants used to prepare catalysts such as (VA) and (VB). Early effortssought to generate free N-heterocyclic carbenes from electron-richolefins known as enetetraamines (Scheme 1, reaction (a)). Unfortunately,these olefins are typically only slightly more air- and light-stablethan their constituent carbenes; they often undergo rapid oxidation insolution. Even when these olefins are oxidatively stable, their thermalcleavage remains debatable, thereby preventing these olefins fromserving as protected carbenes. As an additional drawback, these olefinscleave only at extremely high temperatures that are often incompatiblewith sensitive metal species. The electron-rich nature of enetetraminesalso led to the investigation of their cleavage by reaction withelectrophiles (Scheme 1(b)). Unfortunately, such reactions are generallyunsuitable for use in organometallic synthesis, given the possibility ofdiverse problems. For example, many nucleophilic metal species will nottolerate strong electrophiles (such as CO₂ and SO₂) that are required inthe cleavage reactions. More importantly, the mechanisms of theseelectrophilic reactions remain poorly understood; the choice of optimalelectrophile remains unclear. With these observations, the“electrophilic” route appears ill-suited for a general synthesis ofN-heterocyclic carbene-coordinated metal species.

[0015] An improved method involves the formation of carbene “adducts” bythermal ejection of a leaving group, as illustrated in Scheme 1,reaction (c). In this scheme, the R groups will typically be arylsubstituents (e.g., mesitylene) and an optimal “A” group is CCl₃. Such asynthesis is described by Wanzlick et al. (1961) Chemiche Berichte94:2389-2393, and involves direct condensation ofN,N′-diaryl-1,2-diamines with chloral (trichloroacetaldehyde), animpractical route since chloral is subject to distribution regulations,preventing its widespread availability.

[0016] An improved method for preparing N-heterocyclic carbene reactantsuseful, inter alia, in the synthesis of metal carbene complexes, wouldinvolve readily available reagents, straightforward reaction conditions(e.g., involving non-dry, non-degassed solvents), with generation of anytoxic and/or reactive by-products minimized.

SUMMARY OF THE INVENTION

[0017] The present invention is addressed to the aforementioned needs inthe art, and provides new synthetic routes to metal carbene catalysts,particularly Group 8 transition metal complexes containing aheteroatom-stabilized carbene ligand. Such catalysts, as explainedabove, are highly active catalysts of olefin metathesis reactions, andare advantageous in many respects. The present synthetic methods, whichare “one-pot” syntheses, provide straightforward and convenient routesto obtaining the aforementioned catalysts in high yield using air- andmoisture-stable precursors. The methods are also versatile insofar asthey are generally applicable in the preparation of a variety of mixedligand metal carbene complexes.

[0018] In one aspect of the present invention, a one-pot synthesis isprovided for preparing Group 8 transition metal alkylidene complexes ofthe formula (V)

[0019] M is a Group 8 transition metal, particularly Ru or Os;

[0020] X¹ and X² may be the same or different, and are anionic ligandsor polymers;

[0021] R, R¹ and R² are independently selected from the group consistingof hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containinghydrocarbyl, substituted heteroatom-containing hydrocarbyl, and-(Z)_(n)-Fn where n is zero or 1, Z is a hydrocarbylene, substitutedhydrocarbylene and/or heteroatom-containing hydrocarbylene linkage, andFn is a functional group;

[0022] L is any neutral electron donor ligand; and

[0023] L¹ is a neutral electron donor ligand having the structure offormula (VI)

[0024] X and Y are heteroatoms selected from N, O, S, and P;

[0025] p is zero when X is O or S, and is 1 when X is N or P;

[0026] q is zero when Y is O or S, and is 1 when Y is N or P;

[0027] Q¹, Q², Q³, and Q⁴ are linkers, e.g., hydrocarbylene (includingsubstituted hydrocarbylene, heteroatom-containing hydrocarbylene, andsubstituted heteroatom-containing hydrocarbylene, such as substitutedand/or heteroatom-containing alkylene) or —(CO)—;

[0028] w, x, y and z are independently zero or 1; and

[0029] R³, R^(3A), R⁴, and R^(4A) are independently selected from thegroup consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl,heteroatom-containing hydrocarbyl, and substituted heteroatom-containinghydrocarbyl,

[0030] wherein any two or more of X¹, X², L, R, R¹, R², R³, R^(3A), R⁴,and R^(4A) can be taken together to form a chelating multidentateligand.

[0031] The method involves, initially, combining a metal complexML³(XI)₂, where M and X¹ are as defined above and L³ is a bidentateorganic ligand, with: (a) a salt or adduct of L¹, which serves as aprecursor to the bound ligand (L¹) in the final product; (b) anucleophilic base; and (c) L or a precursor thereto, in (d) the presenceof hydrogen gas, under conditions effective to provide the dihydrogencomplex (VII)

[0032] in a reaction mixture. Upon completion of the reaction andsubsequent cooling, an alkyne of formula (VIII)

[0033] wherein R, R¹, R² and X² are as defined previously, is graduallyadded to the dihydrogen complex. An additional base may be added toneutralize the acid generated during formation of the dihydrogen complex(VII) and/or the nucleophilic base selected is one that is effective inthis regard as well.

[0034] In another aspect of the invention, a method is provided forsynthesizing a ligand precursor L¹-CCl₃ where L¹ is aheteroatom-stabilized carbene ligand as defined above, by contacting anionized, unsaturated analog of L¹ with a non-nucleophilic base in thepresence of chloroform. In a preferred embodiment, the ligand precursorhas the structure of formula (XI)

[0035] in which R³, R⁴, R⁸, R^(8A), R⁹, and R^(9A) are substituentsindependently selected from the group consisting of hydrogen,hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl,substituted heteroatom-containing hydrocarbyl, and -(Z)_(n)-Fn where nis zero or 1, Z is hydrocarbylene, substituted hydrocarbylene and/orheteroatom-containing hydrocarbylene, and Fn is a functional group suchas phosphonato, phosphoryl, phosphanyl, phosphino, sulfonato, C₁-C₂₀alkylsulfanyl, C₅-C₂₀ arylsulfanyl, C₁-C₂₀ alkylsulfonyl, C₅-C₂₀arylsulfonyl, C₁-C₂₀ alkylsulfinyl, C₅-C₂₀ arylsulfinyl, sulfonamido,amino, amido, imino, nitro, nitroso, hydroxyl, C₁-C₂₀ alkoxy, C₅-C₂₀aryloxy, C₂-C₂₀ alkoxycarbonyl, C₅-C₂₀ aryloxycarbonyl, carboxyl,carboxylato, mercapto, formyl, C₁-C₂₀ thioester, cyano, cyanato,carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl, siloxazanyl,boronato, boryl, halogen, stannyl, or germyl, any of which, if thesubstituent permits, may be further substituted with additionalhydrocarbyl and/or -(Z)_(n)-Fn moieties, and further wherein any two ormore of R³, R⁴, R⁸, R^(8A), R⁹, and R^(9A) are optionally linked to forma cyclic group.

[0036] In this embodiment, the synthetic method involves contacting acompound having the structure of formula (XII)

[0037] with chloroform and a non-nucleophilic base effective todeprotonate the chloroform, wherein, in formula (XII), X⁻ is an anioniccounterion such as a halide ion. Examples of non-nucleophilic basesinclude inorganic hydroxides, metal hydrides, and organolithiumreagents.

[0038] In other aspects of the invention, the ligand precursor (XI) isdirectly employed in any of a variety of ligand substitution reactions.For example, precursor (XI) may replace a phosphine ligand in abisphosphine complex such as (XI)(X²)(PR⁵R⁶R⁷)₂M═CRR¹⁴ wherein M, X¹,X², and R are defined previously, R⁵, R⁶ and R⁷ are each independentlyC₅-C₂₀ aryl or C₁-C₁₀ alkyl, including cycloalkyl, and R¹⁴ isindependently selected from the group consisting of hydrogen,hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl,substituted heteroatom-containing hydrocarbyl, and -(Z)_(n)-Fn where n,Z and Fn are defined earlier. In such a reaction, the bisphosphinecomplex is contacted with ligand precursor (XI) under conditionseffective to provide the transition metal carbene complex (XIII)

[0039] The invention also pertains to other such reactions wherein thetrichloromethyl-substituted ligand precursor (XI) is used in an initialligand substitution reaction, which is thereafter followed by one ormore additional synthetic steps, often without need for isolation andpurification of intermediates.

DETAILED DESCRIPTION OF THE INVENTION

[0040] I. Definitions and Nomenclature:

[0041] It is to be understood that unless otherwise indicated thisinvention is not limited to specific reactants, reaction conditions,ligands, metal complexes, or the like, as such may vary. It is also tobe understood that the terminology used herein is for the purpose ofdescribing particular embodiments only and is not intended to belimiting.

[0042] As used in the specification and the appended claims, thesingular forms “a,” “an” and “the” include plural referents unless thecontext clearly dictates otherwise. Thus, for example, reference to “asubstituent” encompasses not only a single substituent but also two ormore substituents that may be the same or different.

[0043] In this specification and in the claims that follow, referencewill be made to a number of terms, which shall be defined to have thefollowing meanings:

[0044] As used herein, the phrase “having the formula” or “having thestructure” is not intended to be limiting and is used in the same waythat the term “comprising” is commonly used.

[0045] The term “alkyl” as used herein refers to a linear, branched orcyclic saturated hydrocarbon group typically although not necessarilycontaining 1 to about 20 carbon atoms, such as methyl, ethyl, n-propyl,isopropyl, n-butyl, isobutyl, t-butyl, octyl, decyl, and the like, aswell as cycloalkyl groups such as cyclopentyl, cyclohexyl and the like.Generally, although again not necessarily, alkyl groups herein contain 1to about 12 carbon atoms. The term “lower alkyl” intends an alkyl groupof 1 to 6 carbon atoms, and the specific term “cycloalkyl” intends acyclic alkyl group, typically having 4 to 8, preferably 5 to 7, carbonatoms. The term “substituted alkyl” refers to alkyl substituted with oneor more substituent groups, and the terms “heteroatom-containing alkyl”and “heteroalkyl” refer to alkyl in which at least one carbon atom isreplaced with a heteroatom. If not otherwise indicated, the terms“alkyl” and “lower alkyl” include linear, branched, cyclic,unsubstituted, substituted, and/or heteroatom-containing alkyl and loweralkyl, respectively.

[0046] The term “alkylene” as used herein refers to a difunctionallinear, branched or cyclic alkyl group, where “alkyl” is as definedabove.

[0047] The term “alkenyl” as used herein refers to a linear, branched orcyclic hydrocarbon group of 2 to 20 carbon atoms containing at least onedouble bond, such as ethenyl, n-propenyl, isopropenyl, n-butenyl,isobutenyl, octenyl, decenyl, tetradecenyl, hexadecenyl, eicosenyl,tetracosenyl, and the like. Preferred alkenyl groups herein contain 2 to12 carbon atoms. The term “lower alkenyl” intends an alkenyl group of 2to 6 carbon atoms, and the specific term “cycloalkenyl” intends a cyclicalkenyl group, preferably having 5 to 8 carbon atoms. The term“substituted alkenyl” refers to alkenyl substituted with one or moresubstituent groups, and the terms “heteroatom-containing alkenyl” and“heteroalkenyl” refer to alkenyl in which at least one carbon atom isreplaced with a heteroatom. If not otherwise indicated, the terms“alkenyl” and “lower alkenyl” include linear, branched, cyclic,unsubstituted, substituted, and/or heteroatom-containing alkenyl andlower alkenyl, respectively.

[0048] The term “alkenylene” as used herein refers to a difunctionallinear, branched or cyclic alkenyl group, where “alkenyl” is as definedabove.

[0049] The term “alkynyl” as used herein refers to a linear or branchedhydrocarbon group of 2 to 20 carbon atoms containing at least one triplebond, such as ethynyl, n-propynyl, and the like. Preferred alkynylgroups herein contain 2 to 12 carbon atoms. The term “lower alkynyl”intends an alkynyl group of 2 to 6 carbon atoms. The term “substitutedalkynyl” refers to alkynyl substituted with one or more substituentgroups, and the terms “heteroatom-containing alkynyl” and“heteroalkynyl” refer to alkynyl in which at least one carbon atom isreplaced with a heteroatom. If not otherwise indicated, the terms“alkynyl” and “lower alkynyl” include linear, branched, unsubstituted,substituted, and/or heteroatom-containing alkynyl and lower alkynyl,respectively.

[0050] The term “alkoxy” as used herein intends an alkyl group boundthrough a single, terminal ether linkage; that is, an “alkoxy” group maybe represented as —O-alkyl where alkyl is as defined above. A “loweralkoxy” group intends an alkoxy group containing 1 to 6 carbon atoms.Analogously, “alkenyloxy” and “lower alkenyloxy” respectively refer toan alkenyl and lower alkenyl group bound through a single, terminalether linkage, and “alkynyloxy” and “lower alkynyloxy” respectivelyrefer to an alkynyl and lower alkynyl group bound through a single,terminal ether linkage.

[0051] The term “aryl” as used herein, and unless otherwise specified,refers to an aromatic substituent containing a single aromatic ring ormultiple aromatic rings that are fused together, directly linked, orindirectly linked (such that the different aromatic rings are bound to acommon group such as a methylene or ethylene moiety), generallycontaining in the range of 5 to 24 carbon atoms. Preferred aryl groupscontain one aromatic ring or 2 to 4 fused or linked aromatic rings,e.g., phenyl, naphthyl, biphenyl, and the like. “Substituted aryl”refers to an aryl moiety substituted with one or more substituentgroups, and the terms “heteroatom-containing aryl” and “heteroaryl”refer to aryl in which at least one carbon atom is replaced with aheteroatom. Unless otherwise indicated, the terms “aromatic,” “aryl,”and “arylene” include heteroaromatic, substituted aromatic, andsubstituted heteroaromatic species.

[0052] The term “aryloxy” as used herein refers to an aryl group boundthrough a single, terminal ether linkage. An “aryloxy” group may berepresented as —O-aryl where aryl is as defined above.

[0053] The term “aralkyl” refers to an alkyl group with an arylsubstituent, and the term “aralkylene” refers to an alkylene group withan aryl substituent; the term “alkaryl” refers to an aryl group that hasan alkyl substituent, and the term “alkarylene” refers to an arylenegroup with an alkyl substituent.

[0054] The term “alicyclic” refers to an aliphatic cyclic moiety, whichmay or may not be bicyclic or polycyclic.

[0055] The term “amino” is used herein to refer to the group —NZ¹Z²,where each of Z¹ and Z² is independently selected from the groupconsisting of hydrogen and optionally substituted alkyl, alkenyl,alkynyl, aryl, aralkyl, alkaryl and heterocyclic.

[0056] The terms “halo,” halide” and halogen” are used in theconventional sense to refer to a chloro, bromo, fluoro or iodosubstituent. The terms “haloalkyl,” “haloalkenyl” or “haloalkynyl” (or“halogenated alkyl,” “halogenated alkenyl,” or “halogenated alkynyl”)refers to an alkyl, alkenyl or alkynyl group, respectively, in which atleast one of the hydrogen atoms in the group has been replaced with ahalogen atom.

[0057] “Hydrocarbyl” refers to univalent hydrocarbyl radicals containing1 to about 30 carbon atoms, preferably 1 to about 20 carbon atoms, mostpreferably 1 to about 12 carbon atoms, including linear, branched,cyclic, saturated and unsaturated species, such as alkyl groups, alkenylgroups, aryl groups, and the like. The term “lower hydrocarbyl” intendsa hydrocarbyl group of 1 to 6 carbon atoms, and the term“hydrocarbylene” intends a divalent hydrocarbyl moiety containing 1 toabout 30 carbon atoms, preferably 1 to about 20 carbon atoms, mostpreferably 1 to about 12 carbon atoms, including linear, branched,cyclic, saturated and unsaturated species. The term “lowerhydrocarbylene” intends a hydrocarbylene group of 1 to 6 carbon atoms.“Substituted hydrocarbyl” refers to hydrocarbyl substituted with one ormore substituent groups, and the terms “heteroatom-containinghydrocarbyl” and “heterohydrocarbyl” refer to hydrocarbyl in which atleast one carbon atom is replaced with a heteroatom. Similarly,“substituted hydrocarbylene” refers to hydrocarbylene substituted withone or more substituent groups, and the terms “heteroatom-containinghydrocarbylene” and heterohydrocarbylene” refer to hydrocarbylene inwhich at least one carbon atom is replaced with a heteroatom. Unlessotherwise indicated, the term “hydrocarbyl” and “hydrocarbylene” are tobe interpreted as including substituted and/or heteroatom-containinghydrocarbyl and hydrocarbylene moieties, respectively.

[0058] The term “heteroatom-containing” as in a “heteroatom-containinghydrocarbyl group” refers to a hydrocarbon molecule or a hydrocarbylmolecular fragment in which one or more carbon atoms is replaced with anatom other than carbon, e.g., nitrogen, oxygen, sulfur, phosphorus orsilicon, typically nitrogen, oxygen or sulfur. Similarly, the term“heteroalkyl” refers to an alkyl substituent that isheteroatom-containing, the term “heterocyclic” refers to a cyclicsubstituent that is heteroatom-containing, the terms “heteroaryl” andheteroaromatic” respectively refer to “aryl” and “aromatic” substituentsthat are heteroatom-containing, and the like. It should be noted that a“heterocyclic” group or compound may or may not be aromatic, and furtherthat “heterocycles” may be monocyclic, bicyclic, or polycyclic asdescribed above with respect to the term “aryl.”

[0059] “substituted” as in “substituted hydrocarbyl,” “substitutedalkyl,” “substituted aryl,” and the like, as alluded to in some of theaforementioned definitions, is meant that in the hydrocarbyl, alkyl,aryl, or other moiety at least one hydrogen atom bound to a carbon (orother) atom is replaced with one or more non-hydrogen substituents.Examples of such substituents include, without limitation: functionalgroups such as halogen, phosphonato, phosphoryl, phosphanyl, phosphino,sulfonato, C₁-C₂₀ alkylsulfanyl, C₅-C₂₀ arylsulfanyl, C₁-C₂₀alkylsulfonyl, C₅-C₂₀ arylsulfonyl, C₁-C₂₀ alkylsulfinyl, C₅-C₂₀arylsulfinyl, sulfonamido, amino, amido, imino, nitro, nitroso,hydroxyl, C₁-C₂₀ alkoxy, C₅-C₂₀ aryloxy, C₂-C₂₀ alkoxycarbonyl, C₅-C₂₀aryloxycarbonyl, carboxyl, carboxylato, mercapto, formyl, C₁-C₂₀thioester, cyano, cyanato, carbamoyl, epoxy, styrenyl, silyl, silyloxy,silanyl, siloxazanyl, boronato, or boryl, or a metal-containing ormetalloid-containing group (wherein the metal may be, for example, Sn orGe); and the hydrocarbyl moieties C₁-C₂₀ alkyl, C₂-C₂₀ alkenyl, C₂-C₂₀alkynyl, C₅-C₂₀ aryl, C₅-C₃₀ aralkyl, and C₅-C₃₀ alkaryl.

[0060] In addition, the aforementioned functional groups may, if aparticular group permits, be further substituted with one or moreadditional functional groups or with one or more hydrocarbyl moietiessuch as those specifically enumerated above. Analogously, theabove-mentioned hydrocarbyl moieties may be further substituted with oneor more functional groups or additional hydrocarbyl moieties such asthose specifically enumerated.

[0061] When the term “substituted” appears prior to a list of possiblesubstituted groups, it is intended that the term apply to every memberof that group. That is, the phrase “substituted alkyl, alkenyl andalkynyl” is to be interpreted as “substituted alkyl, substituted alkenyland substituted alkynyl.” Similarly, “optionally substituted alkyl,alkenyl and alkynyl” is to be interpreted as “optionally substitutedalkyl, optionally substituted alkenyl and optionally substitutedalkynyl.”

[0062] “Optional” or “optionally” means that the subsequently describedcircumstance may or may not occur, so that the description includesinstances where the circumstance occurs and instances where it does not.For example, the phrase “optionally substituted” means that anon-hydrogen substituent may or may not be present on a given atom, and,thus, the description includes structures wherein a non-hydrogensubstituent is present and structures wherein a non-hydrogen substituentis not present.

[0063] In the molecular structures herein, the use of bold and dashedlines to denote particular conformation of groups follows the IUPACconvention. A bond indicated by a broken line indicates that the groupin question is below the general plane of the molecule as drawn (the “α”configuration), and a bond indicated by a bold line indicates that thegroup at the position in question is above the general plane of themolecule as drawn (the “β” configuration).

[0064] II. General Description of the Ligands and Catalysts Synthesized:

[0065] The methods of the present invention may be used to synthesizeGroup 8 transition metal carbene complexes that include a metal centerin a +2 oxidation state, have an electron count of 16, and arepenta-coordinated. More specifically, the methods of the presentinvention are useful in synthesizing compounds having the structure offormula (V)

[0066] as well as compounds that serve as precursors to L¹ in thesynthesis of complex (V). The various substituents are as follows:

[0067] M, which serves as the transition metal center in the +2oxidation state, is a Group 8 transition metal, particularly rutheniumor osmium. In a preferred embodiment, M is ruthenium.

[0068] X¹ and X² may be the same or different, and are anionic ligandsor polymers, and may be linked together to form a cyclic group,typically although not necessarily a five- to eight-membered ring. Inpreferred embodiments, X¹ and X² are each independently hydrogen,halide, or one of the following groups: C¹-C₂₀ alkyl, C₅-C₂₀ aryl,C₁-C₂₀ alkoxy, C₅-C₂₀ aryloxy, C₃-C₂₀ alkyldiketonate, C₅-C₂₀aryldiketonate, C₂-C₂₀ alkoxycarbonyl, C₅-C₂₀ aryloxycarbonyl, C₂-C₂₀acyl, C₁-C₂₀ alkylsulfonato, C₅-C₂₀ arylsulfonato, C₁-C₂₀ alkylsulfanyl,C₅-C₂₀ arylsulfanyl, C₁-C₂₀ alkylsulfinyl, or C₅-C₂₀ arylsulfinyl.Optionally, X¹ and X² may be substituted with one or more moietiesselected from the group consisting of C₁-C₁₀ alkyl, C₁-C₁₀ alkoxy, aryl,and halide, which may, in turn, with the exception of halide, be furthersubstituted with one or more groups selected from halide, C₁-C₆ alkyl,C₁-C₆ alkoxy, and phenyl. In more preferred embodiments, X¹ and X² arehalide, benzoate, C₂-C₆ acyl, C₂-C₆ alkoxycarbonyl, C₁-C₆ alkyl,phenoxy, C₁-C₆ alkoxy, C₁-C₆ alkylsulfanyl, C₅-C₂₀ aryl, or C₁-C₆alkylsulfonyl. In even more preferred embodiments, X¹ and X² are eachhalide, CF₃CO₂, CH₃CO₂, CFH₂CO₂, (CH₃)₃CO, (CF₃)₂(CH₃)CO, (CF₃)(CH₃)₂CO,PhO, MeO, EtO, tosylate, mesylate, or trifluoromethanesulfonate. In themost preferred embodiments, X¹ and X² are each chloride. The complex mayalso be attached to a solid support, such as to a polymeric substrate,and this attachment may be effected by means of X¹ and/or X², in whichcase X¹ and/or X² is a polymer.

[0069] R, R¹ and R² are selected from the group consisting of hydrogen,hydrocarbyl (e.g., alkyl, alkenyl, alkynyl, aryl, aralkyl, alkaryl,etc.), substituted hydrocarbyl (e.g., substituted alkyl, alkenyl,alkynyl, aryl, aralkyl, alkaryl, etc.), heteroatom-containinghydrocarbyl (e.g., heteroatom-containing alkyl, alkenyl, alkynyl, aryl,aralkyl, alkaryl, etc.), and substituted heteroatom-containinghydrocarbyl (e.g., substituted heteroatom-containing alkyl, alkenyl,alkynyl, aryl, aralkyl, alkaryl, etc.), and -(Z)_(n)-Fn where n, Z andFn are defined previously. R¹ and R² may also be linked to form a cyclicgroup, which may be aliphatic or aromatic, and may contain substituentsand/or heteroatoms. Generally, such a cyclic group will contain 4 to 12,preferably 5 to 8, ring atoms.

[0070] In preferred catalysts, R is hydrogen and R¹ and R² are selectedfrom the group consisting of hydrogen, C₁-C₂₀ alkyl, C₅-C₂₀ aryl, and-(Z)_(n)-Fn where Z is alkylene or substituted alkylene, and Fn isphosphonato, phosphoryl, phosphanyl, phosphino, sulfonato, C₁-C₂₀alkylsulfanyl, C₅-C₂₀ arylsulfanyl, C¹-C₂₀ alkylsulfonyl, C₅-C₂₀arylsulfonyl, C¹-C₂₀ alkylsulfinyl, C₅-C₂₀ arylsulfinyl, sulfonamido,amino, amido, imino, nitro, nitroso, hydroxyl, C₁-C₂₀ alkoxy, C₅-C₂₀aryloxy, C₂-C₂₀ alkoxycarbonyl, C₅-C₂₀ aryloxycarbonyl, carboxyl,carboxylato, mercapto, formyl, C₁-C₂₀ thioester, cyano, cyanato,carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl, siloxazanyl,boronato, boryl, halogen, stannyl, or germyl. More preferably, R¹ and R²are selected from the group consisting of hydrogen, C₁-C₆ alkyl, andC₅-C₂₀ aryl.

[0071] L is any neutral electron donor ligand, and may or may not belinked to R² or other substituents within the complex. Examples ofsuitable L moieties include, without limitation, phosphine, sulfonatedphosphine, phosphite, phosphinite, phosphonite, arsine, stibine, ether(including cyclic ethers), amine, amide, imine, sulfoxide, carboxyl,nitrosyl, pyridine, substituted pyridine (e.g., halogenated pyridine),imidazole, substituted imidazole (e.g., halogenated imidazole), pyrazine(e.g., substituted pyrazine), and thioether. In more preferredembodiments, L is a phosphine of the formula PR⁵R⁶R⁷, where R⁵, R⁶, andR⁷ are each independently C₅-C₂ aryl or C₁C₁₀ alkyl, particularlyphenyl, primary alkyl, secondary alkyl or cycloalkyl. In the mostpreferred embodiments, L is selected from the group consisting of—P(cyclohexyl)₃, —P(cyclopentyl)₃, —P(isopropyl)₃, —P(phenyl)₃,—P(phenyl)₂(R⁷) and —P(phenyl)(R⁷)₂, in which R⁷ is alkyl, typicallylower alkyl. Also preferred are weaker ligands such as thenitrogen-containing heterocycles, which enhance catalytic activitypresumably because of the requirement that the L ligand dissociate forinitiation to occur. Examples of complexes wherein L and R² are linkedinclude the following:

[0072] L¹ is a neutral electron donor ligand having the structure offormula (VI)

[0073] wherein X, Y, p, q, Q¹, Q², Q³, Q⁴, R³, R^(3A), R⁴, R^(4A), w, x,y and z are as follows:

[0074] X and Y are heteroatoms typically selected from N, O, S, and P.Since O and S are divalent, p is necessarily zero when X is O or S, andq is necessarily zero when Y is O or S. However, when X is N or P, thenp is 1, and when Y is N or P, then q is 1. In a preferred embodiment,both X and Y are N.

[0075] Q¹, Q², Q³, and Q⁴ are linkers, e.g., hydrocarbylene (includingsubstituted hydrocarbylene, heteroatom-containing hydrocarbylene, andsubstituted heteroatom-containing hydrocarbylene, such as substitutedand/or heteroatom-containing alkylene) or —(CO)—, and w, x, y and z areindependently zero or 1, meaning that each linker is optional.Preferably, w, x, y and z are all zero.

[0076] R³, R^(3A), R⁴, and R^(4A) are independently selected from thegroup consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl,heteroatom-containing hydrocarbyl, and substituted heteroatom-containinghydrocarbyl, wherein R^(3A) and R^(4A) may be linked to form a cyclicgroup.

[0077] It should be emphasized that any two or more (typically two,three or four) of X¹, X², L, R¹, R², R³, R^(3A), R⁴, and R^(4A) can betaken together to form a chelating multidentate ligand, as disclosed,for example, in U.S. Pat. No. 5,312,940 to Grubbs et al. Examples ofbidentate ligands include, but are not limited to, bisphosphines,dialkoxides, alkyldiketonates, and aryldiketonates. Specific examplesinclude —P(Ph)₂CH₂CH₂P(Ph)₂—, —As(Ph)₂CH₂CH₂As(Ph₂)—,—P(Ph)₂CH₂CH₂C(CF₃)₂O—, binaphtholate dianions, pinacolate dianions,—P(CH₃)₂(CH₂)₂P(CH₃)₂— and —OC(CH₃)₂(CH₃)₂CO—. Preferred bidentateligands are —P(Ph)₂ CH₂CH₂P(Ph)₂— and —P(CH₃)₂(CH₂)₂P(CH₃)₂—. Tridentateligands include, but are not limited to,(CH₃)₂NCH₂CH₂P(Ph)CH₂CH₂N(CH₃)₂. Other preferred tridentate ligands arethose in which any three of X¹, X², L, R¹, R², R³, R^(3A), R⁴, andR^(4A) (e.g., X, L, and any one of R³, R^(3A), R⁴, and R^(4A)) are takentogether to be cyclopentadienyl, indenyl or fluorenyl, each optionallysubstituted with C₂-C₂₀ alkenyl, C₂-C₂₀ alkynyl, C₁-C₂₀ alkyl, C₅-C₂₀aryl, C¹-C₂₀ alkoxy, C₂-C₂₀ alkenyloxy, C₂-C₂₀ alkynyloxy, C₅-C₂₀aryloxy, C₂-C₂₀ alkoxycarbonyl, C₁-C₂₀ alkylthio, C₁-C₂₀ alkylsulfonylor C₁-C₂₀ alkylsulfinyl, each of which may be further substituted withC₁-C₆ alkyl, halogen, C₁-C₆ alkoxy or with a phenyl group optionallysubstituted with halogen, C₁-C₆ alkyl or C₁-C₆ alkoxy. More preferably,in compounds of this type, X, L, and any one of R³, R^(3A), R⁴, andR^(4A) are taken together to be cyclopentadienyl or indenyl, eachoptionally substituted with vinyl, C₁-C₁₀ alkyl, C₅-C₂₀ aryl, C₁-C₁₀carboxylate, C₂-C₁₀ alkoxycarbonyl, C₁C₁₀ alkoxy, C₅-C₂₀ aryloxy, eachoptionally substituted with C₁-C₆ alkyl, halogen, C₁-C₆ alkoxy or with aphenyl group optionally substituted with halogen, C₁-C₆ alkyl or C₁-C₆alkoxy. Most preferably, X, L, and any one of R³, R^(3A), R⁴, and R^(4A)may be taken together to be cyclopentadienyl, optionally substitutedwith vinyl, hydrogen, Me or Ph. Tetradentate ligands include, but arenot limited to O₂C(CH₂)₂P(Ph)(CH₂)₂P(Ph)(CH₂)₂CO₂, phthalocyanines, andporphyrins.

[0078] In a preferred embodiment, w, x, y and z are zero, X and Y are N,and R^(3A) and R^(4A) are linked to form —Q—, such that L¹ has thestructure of formula (IX)

[0079] wherein Q is a hydrocarbylene, substituted hydrocarbylene,heteroatom-containing hydrocarbylene, or substitutedheteroatom-containing hydrocarbylene linker, and further wherein two ormore substituents on adjacent atoms within Q may be linked to form anadditional cyclic group, which may be similarly substituted to provide afused polycyclic structure of two to five cyclic groups. Q is often,although again not necessarily, a two-atom linkage or a three-atomlinkage, e.g., —CH₂—CH₂—, —CH(Ph)—CH(Ph)— where Ph is phenyl; ═CR—N═,giving rise to an unsubstituted (when R=H) or substituted (R=other thanH) triazolyl group; and —CH₂—SiR₂—CH₂— (where R is H, alkyl, alkoxy,etc.).

[0080] In a more preferred embodiment, Q is a two-atom linkage havingthe structure —CR⁸R^(8A)—CR⁹R^(9A)— or —CR⁸═CR⁹—, more preferably—CR⁸R^(8A)—CR⁹R^(9A)—, in which case the complex has the structure offormula (XIV)

[0081] wherein R⁸, R^(8A), R⁹, and R^(9A) are independently selectedfrom the group consisting of hydrogen, hydrocarbyl, substitutedhydrocarbyl, heteroatom-containing hydrocarbyl, substitutedheteroatom-containing hydrocarbyl, and may comprise a functional groupFn as defined previously. Preferred R⁸, R^(8A), R⁹, and R^(9A) moietiesinclude, without limitation, C₁-C₂₀ alkyl, C₂-C₂₀ alkenyl, C₂-C₂₀alkynyl, C₅-C₂₀ aryl, carboxyl, C₁-C₂₀ alkoxy, C₂-C₂₀ alkenyloxy, C₂-₂₀alkynyloxy, C₅-C₂₀ aryloxy, C₂-C₂₀ alkoxycarbonyl, C₂-C₂₀alkoxycarbonyl, C₁-C₂₀ alkylthio, C₅-C₂₀ arylthio, C₁-C₂₀ alkylsulfonyl,and C₁-C₂₀ alkylsulfinyl, optionally substituted with one or moremoieties selected from the group consisting of C₁-C₁₀ alkyl, C₁-C₁₀alkoxy, C₅-C₂₀ aryl, hydroxyl, sulfhydryl, —(CO)—H, and halide.

[0082] Additionally, any two of R⁸, R^(8A), R⁹, and R^(9A) may be linkedtogether to form a substituted or unsubstituted, saturated orunsaturated ring structure, e.g., a C₄-C₁₂ alicyclic group or a C₅ or C₆aryl group, which may itself be substituted, e.g., with linked or fusedalicyclic or aromatic groups, or with other substituents.

[0083] Examples of N-heterocyclic carbene ligands incorporated intocomplex (X) thus include, but are not limited to, the following:

[0084] R³ and R⁴ are preferably aromatic, substituted aromatic,heteroaromatic, substituted heteroaromatic, alicyclic, or substitutedalicyclic, composed of from one to about five cyclic groups. When R³ andR⁴ are aromatic, they are typically although not necessarily composed ofone or two aromatic rings, which may or may not be substituted, e.g., R³and R⁴ may be phenyl, substituted phenyl, biphenyl, substitutedbiphenyl, or the like. In one preferred embodiment, R³ and R⁴ are thesame and have the structure (X)

[0085] in which R¹⁰, R¹¹, and R¹² are each independently hydrogen,C₁-C₂₀ alkyl, substituted C₁-C₂₀ alkyl, C₁-C₂₀ heteroalkyl, substitutedC₁-C₂₀ heteroalkyl, C₅-C₂₀ aryl, substituted C₅-C₂₀ aryl, C₅-C₂₀heteroaryl, C₅-C₃₀ aralkyl, C₅-C₃₀ alkaryl, or halogen. In especiallypreferred embodiments, R¹⁰, R¹¹, and R¹² are each independently selectedfrom the group consisting of hydrogen, methyl, ethyl, propyl, isopropyl,hydroxyl, halogen, phenyl, and lower alkyl-substituted phenyl. In themost preferred embodiments, R¹⁰, R¹¹, and R¹² are the same and are eachmethyl.

[0086] Other catalysts may also be synthesized using the presentmethods, as will be discussed in detail infra. Such catalysts includeanalogs of alkylidene (V) wherein the M═CR—CH═CR¹R² moiety is replacedwith M═CRR¹⁴ wherein R¹⁴ does not necessarily comprise a vinyl group,e.g., it may be alkyl or aryl, and in a preferred embodiment is phenyl.Other complexes that may be synthesized using the methods of theinvention are vinylidene analogs of (V) wherein the M═CR—CH═CR¹R² moietyis replaced with M═C═CHR. Both of the latter analogs are readilyprepared using a “chloroform adduct” of a carbene ligand, i.e., atrichloromethyl-substituted precursor to a carbene ligand.

[0087] III. One-Pot Synthesis of Transition Metal Alkylidenes:

[0088] One embodiment of the invention pertains to a method forsynthesizing transition metal alkylidene complexes having the structureof formula (V)

[0089] in which the various substituents are defined earlier herein. Thesynthesis is a two-step reaction involving formation of a transitionmetal dihydrogen complex substituted with the desired carbene ligand,followed by reaction with an alkyne to yield the metal alkylidenefunctionality.

[0090] A. Formation of the Dihydrogen Complex Intermediate:

[0091] In the initial step of the synthesis, a metal complex ML³(XI)₂,where M and X¹ are as defined above and L³ is a bidentate organicligand, is contacted with: (a) a salt or adduct of L¹, which serves as aprecursor to the bound ligand (L¹) in the final product; (b) anucleophilic base; and (c) L or a precursor thereto, in (d) the presenceof hydrogen gas, under conditions effective to provide the dihydrogencomplex (VII)

[0092] in a reaction mixture. An additional base may be added toneutralize the acid generated during formation of (VII) and/or thenucleophilic base selected is one that is effective in this regard aswell.

[0093] The nucleophilic base is generally a nitrogenous base with somesteric bulk, as some degree of steric encumbrance typically increasesthe yield of the dihydrogen complex and minimizes generation of othermetal hydride species. Preferred nucleophilic bases contain secondary ortertiary alkyl moieties, cycloalkyl moieties, aryl groups,tri(alkyl)silyl groups, or the like, and particularly preferrednucleophilic bases have the structure M¹N(SiR¹⁵ ₃)₂ wherein M¹ is analkali metal, preferably potassium, and R¹⁵ is hydrocarbyl, typicallylower hydrocarbyl, and thus includes the lower alkyl groups methyl,ethyl, n-propyl, cyclohexyl. Such bases are more effective in thepresent method when a nonpolar organic solvent such as benzene, toluene,hexane, or the like is employed for the reaction. In addition, withnucleophilic bases of the formula M¹N(SiR^(X) ₃)₂, there is generally noneed for an additional base to remove the acid generated duringformation of the dihydrogen complex, insofar as the HN(SiR^(x) ₃)₂generated from the deprotonation of the salt or ligand of L¹ (e.g.,IMesH₂Cl), is typically sufficient to remove the acid (e.g., HCl)produced.

[0094] In a preferred embodiment, the salt or adduct of L¹ is a halidesalt, e.g., a chloride salt, or a trichloromethyl-substituted carbeneprecursor as described in part (IV) of this section, infra. The ligandL³ may be virtually any bidentate ligand that can detach in a ligandsubstitution reaction with the salt or adduct of L¹. Examples of ligandssuitable as L³ include C₅-C₈ cyclic dienes, optionally substitutedand/or heteroatom containing. A particularly preferred L³ is1,5-cyclooctadiene.

[0095] Elevated temperatures are generally necessary, on the order of55° C. to 90° C., although it will be appreciated that an optimumtemperature for any particular reaction will depend on the selectedstarting materials. Hydrogen pressure in the reaction chamber willgenerally be maintained at about 20 psi to 30 psi, although the hydrogenpressure is not critical. The progress of the reaction may be monitoredvia NMR or using any other suitable means.

[0096] After cooling, the dihydrogen complex (VII) may be used in theremaining step of the synthesis without isolation and purification,since (VII) is routinely produced in high yield without a significantfraction of other metal hydrides. However, if desired, the dihydrogencomplex can be isolated and purified at this point using conventionalmeans, e.g., by column chromatography on silica gel.

[0097] B. Formation of the Dihydrogen Complex:

[0098] The second step of the reaction involves formation of thealkylidene at the transition metal center. Following preparation of(VII), cooling, and optional isolation and purification of thedihydrogen complex as described in (A), above, an alkyne of formula(VIII) is

[0099] slowly added to the dihydrogen complex (which may be in thereaction mixture following its preparation in (A), or, if the complexhas been isolated and purified, may be in solution in a suitablesolvent). This reaction is generally, although not necessarily, carriedout at a temperature in the range of about 5° C. to about 30° C. Informula (VIII), R, R¹, R² and X² are as defined previously.

[0100] Suitable alkynes for carrying out this reaction are described inU.S. Pat. Publication No. 2002/0022733 A1 to Grubbs et al., and include,by way of example, compounds of formula (VIII) wherein R is hydrogen,C₁-C₂₀ alkyl, or C₅-C₂₀ aryl, X¹ is halide, and R¹ and R² are eachC₁-C₂₀ alkyl, C₅-C₂₀ aryl, C₁-C₂₀ alkoxy, C₅-C₂₀ aryloxy, C₁-C₂₀alkylsulfanyl, C₅-C₂₀ arylsulfanyl, C₁-C₂₀ alkylsulfinyl, C₅-C₂₀arylsulfinyl, and may comprise functional groups Fn wherein Fn isdefined previously. For any of the R, R¹ and R² moieties that permitfurther substitution, such moieties may further include substituentsand/or heteroatoms that do not adversely affect the desired reaction.Particularly preferred alkynes are the propargylic halidesH—C≡C—C(CH₃)₂X¹ wherein X¹ is halo, e.g., chloro or bromo.

[0101] The reaction between the alkyne and the dihydrogen complex (VII)proceeds quickly, even at a low temperatures. See Example 1, whichdescribes synthesis of the alkylidene complex(PCy₃)(IMesH₂)Cl₂Ru═CH—CH═C(CH₃)₂ (2) via the dihydrogen complex(PCy₃)(IMesH₂)Ru(H)(H₂)Cl (1). Following formation of (1), addition ofpropargyl chloride resulted in a nearly instantaneous reaction, yieldingthe desired alkylidene complex (2) in >95% yield. Reactions with otheralkynes, particularly propargylic halides, also proceed rapidly andafford high yields of the transition metal alkylidene product.

[0102] IV. Preparation of “Chloroform Adducts” As Carbene LigandPrecursors:

[0103] In another embodiment, a method is provided for synthesizing atrichloromethyl-substituted ligand precursor having the structureL¹-CCl₃ wherein L¹ is defined in part (I) of this section. In apreferred embodiment, the ligand precursor L¹-CCl₃ has the structure(XI)

[0104] in which R³, R⁴, R⁸, R^(8A), R⁹, and R^(9A) are as definedpreviously. This ligand precursor, or “chloroform adduct,” is an optimalprecursor to L¹ in the synthesis described in part (III), above. Thatis, compound (XI) serves as the salt or adduct of L¹ that is combinedwith the metal complex, the nucleophilic base, and L.

[0105] In this embodiment, an ionized, unsaturated analog of L¹ isreacted with chloroform and a base. In a preferred embodiment, compound(XI) is synthesized by contacting a compound having the structure offormula (XII)

[0106] (i.e., the ionized, unsaturated analog of L¹) with chloroform anda non-nucleophilic base effective to deprotonate the chloroform.Suitable bases include inorganic hydroxides, metal hydrides, andorganolithium reagents such as t-butyllithium. Inorganic hydroxidesinclude, by way of example, alkali metal hydroxides, alkaline earthmetal hydroxides, e.g., sodium hydroxide, calcium hydroxide, potassiumhydroxide, magnesium hydroxide, and the like. Preferred inorganichydroxides are potassium hydroxide and sodium hydroxide, with potassiumhydroxide particularly preferred. Metal hydrides include, but are notlimited to, sodium hydride, lithium hydride, potassium hydride, rubidiumhydride, cesium hydride, magnesium hydride, calcium hydride, strontiumhydride, barium hydride, aluminum hydride, and combinations thereof. Themetal hydride is preferably sodium hydride. Metal hydrides also includemetal borohydrides, for example, lithium borohydride, potassiumborohydride and sodium borohydride, although sodium hydride isparticularly preferred. Organolithium reagents, as will be appreciatedby those of ordinary skill in the art, include alkyllithium reagentssuch as methyl lithium, isopropyl lithium, n-butyllithium,s-butyllithium, t-butyllithium, and the like, as well as aryllithiumlithium reagents, e.g., phenyl lithium and p-tolyl lithium.

[0107] The reaction will generally be carried out for a time period ofabout 0.5 to 4 hours at ambient temperature, although elevatedtemperatures may be beneficial or required under certain conditions. Thechloroform may serve as the solvent, or an additional solvent may beemployed. Any organic solvent can be used providing that there is noadverse impact on the desired reaction and that the reactants aresufficiently soluble therein. Suitable solvents include, solely by wayof example, benzene, toluene, and tetrahydrofuran.

[0108] A series of experiments was carried out to evaluate the effect ofvarious parameters on the aforementioned reaction, as described inExample 6. Chloroform was deprotonated with a variety ofnon-nucleophilic bases (including alkali metal hydroxides) and theresulting solution was added to the chloride 4,5-dihydroimidazolium salt(IMesH₂Cl) under varying temperatures and solvent conditions (Table 1).TABLE 1 Variation of reaction parameters for the nucleophilic additionof trichloromethyl anion to 4,5-dihydroimidazolium salts.^(a)

Number of Reaction equiv. CHCl₃ Solvent Base Temperature Time Yield Assolvent CHCl₃ NaOH 25° C.   2 hr. 54% 3.0 THF NaOH reflux   2 hr. 59%3.0 C₆H₆ NaOH 25° C. 1.5 hr. 67% 3.0 toluene KOH 25° C.   2 hr.

[0109] After purification by recrystallization or column chromatography,the IMesH₂.CHCl₃ adduct could be isolated on the gram scale in 83-90%yields as pure crystalline material. This high-yielding adductsynthesis, using the easily handled base potassium hydroxide, representsthe simplest procedure developed to date for the production ofIMesH₂.CHCl₃ and analogs thereof. The synthesis can be readily carriedout on the benchtop with non-dry, non-degassed solvents, and the use ofpotassium hydroxide prevents any large-scale flammability or reactivityproblems. Exposure to potentially toxic chlorinated solvents (i.e.chloroform) in this procedure is also kept to a minimum.

[0110] As noted above, it is also possible to deprotonate chloroformwith even stronger non-nucleophilic bases such as organolithium reagents(tert-butyllithium) and florene. These examples are noteworthy for theirsolubility in other non-polar solvents (such as hexanes or diethylether) which may be used. In a variety of cases these nonpolar solventsshould be ideal to limit the solubility of the imidazolium salt, therebyminimizing the side reactions from dichlorocarbene formed in thereaction.

[0111] The aforementioned adduct synthesis was also found to be tolerantof a variety of substitution patterns on the 4,5-dihydro-imidazoliumsalt, including R³ and/or R⁴=substituted aryl and R⁸ and/or R⁹=aryl oralkyl (in structural formula (XI)). It is relevant to note that only4,5-dihydroimidazolium salts form imidazolidenes —the aromaticimidazolium salts (i.e., the unsaturated analogs) never form theseadducts under any conditions. Instead, the latter species undergoimmediate deprotonation to directly form the free carbene.

[0112] An alternate way of obtaining the compound IMesH₂.CHCl₃ is by thereaction of an equimolar amount of a strong base such as sodium hydridewith chloroform in the presence of the salt (II), as described inExample 4, part (a). By this route, higher yield and purity of theobtained product is achievable, eliminating any further purification.This reaction is relatively rapid and takes place at room temperature.The trichloromethyl anion is formed in low concentrations from thereaction of a strong base with chloroform itself. This can bepre-formed, standardized and stored for short a period at lowtemperature to prevent the formation of dichlorocarbene. Chloroform isalso conveniently used as a single component recyclable system becausebis-mesityl-imidazolium chloride and like compounds are soluble in it,thus acting as a solvent and reactant the entire reaction. If equimolaramounts of base and imidazolium (or other) salt are dissolved inchloroform, upon dissolution of the base, the trichloromethyl anion isformed and is readily uptaken by the imidazolium salt. In a few minutes,the base is depleted and the resulting product remains in solution whilesodium chloride (the only solid byproduct) falls out of solution. Thisway, the byproducts are minimized, maximizing the yield and avoidingfurther purification.

[0113] Once the adduct (XI) is obtained in large quantity by thedescribed method, it may be directly employed in a variety of ligandsubstitution reactions. In one embodiment, ligand precursor (XI) mayreplace a phosphine ligand in a bisphosphine complex such as(XI)(X²)(PR⁵R⁶R⁷)₂M═CRR¹⁴, below,

[0114] wherein M is Ru or Os, typically Ru, X¹ and X² are halides orother anionic ligands, R⁵, R⁶, and R⁷ are each independently aryl orC₁-C₁₀ alkyl, including cycloalkyl, R is as defined previously, and R¹⁴is independently selected from the group consisting of hydrogen,hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl,substituted heteroatom-containing hydrocarbyl, and -(Z)_(n)-Fn where n,Z and Fn are defined earlier. In such a reaction, the bisphosphinecomplex is contacted with ligand precursor (XI) under conditionseffective to provide the transition metal carbene complex (XIII)

[0115] As demonstrated in Table 2, the rate of this substitutionreaction is strongly temperature-dependent. In general, the reactiondoes not proceed at any appreciable rate below 55° C. At 80° C., thesubstitution rate remains much slower than the rate of phosphinedissociation, suggesting that the rate-limiting step in these reactionsis the decomposition of IMesH₂.CHCl₃ to the free carbene. Even at thesehigh temperatures the ruthenium species appear to remain intactthroughout the reaction, without the formation of hydrides or otherbyproducts. TABLE 2 Ligand Substitution on ruthenium(II) metathesiscatalysts.^(a)

Number of equiv. Concentration of Reaction Rate IMesH₂.CHCl₃IMesH₂.CHCl₃ Temperature (k_(obs) × 10⁴, s⁻¹)^(b) 1.0 0.04 M 40° C. NA1.0 0.04 M 60° C. 8.53 ± 0.33 2.0 0.08 M 60° C. 7.23 ± 0.12 5.0 0.20 M60° C. 28.8 ± 2.6  5.0 0.20 M 80° C. 326 ± 14 

[0116] Another example of a ligand substitution reaction in which theligand precursor (XI) has utility is in the synthesis of a transitionmetal alkylidene complex of formula (XIV)

[0117] wherein M, X¹, X², L, R, R¹, R², R³, R⁴, R⁸, R^(8A), R⁹, andR^(9A) are as defined previously. The method circumvents the need for anexcess of the salt or adduct of L¹ (e.g., IMesH₂Cl) used as a startingmaterial in the direct substitution reaction described in part (III) ofthis section (see Example 4). In this embodiment, the route towards thetransition metal alkylidene complex (XIV) is carried out as follows.

[0118] Initially, the ligand precursor (XI)

[0119] is contacted with a metal complex M(XI)₂(L⁴)₂, wherein X¹ is asdefined previously and L⁴ is an eta-6 coordinating ligand, e.g., anaromatic or substituted aromatic ligand such as p-cymene, under an inertatmosphere for a time period effective to allow the ligand substitutionreaction to go to completion. The intermediate thereby provided, havingthe structure of formula (XV)

[0120] is then reacted with P(R⁵R⁶R⁷) in the presence of hydrogen and abase, to give the dihydrogen complex (XVI)

[0121] which is then treated with an alkyne of the formula (VIII)

[0122] wherein R, R¹, R² and X² are as defined previously, as describedin part (III) of this section.

[0123] The aforementioned method may be modified to provide a transitionmetal vinylidene product in lieu of the alkylidene (XIV). The vinylideneproduct will generally have the structure of formula (XVII)

[0124] wherein M, X¹, X², L, R³, R⁴, R⁸, R^(8A), R⁹, and R^(9A) are asdefined previously, and R¹³ is selected from the group consisting ofhydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containinghydrocarbyl, substituted heteroatom-containing hydrocarbyl, and-(Z)_(n)-Fn where n is zero or 1, Z is a hydrocarbylene linkage, and Fnis a functional group.

[0125] This synthesis is a one-step method wherein intermediate (XV) isprepared as described above, and then directly treated with an alkyne offormula H—C≡C—R¹³ and a tri-substituted phosphine (or other anionicligand precursor).

[0126] It is to be understood that while the invention has beendescribed in conjunction with the preferred specific embodimentsthereof, that the foregoing description as well as the examples thatfollow are intended to illustrate and not limit the scope of theinvention. It will be appreciated that various modifications may be madeto the methodology of the invention, e.g., with respect to reactionconditions, starting materials, substituents, and the like, which willbe recognized by those of ordinary skill in the art as within the spiritand scope of the invention.

[0127] All patents, patent applications, and publications mentionedherein are hereby incorporated by reference in their entireties.

EXPERIMENTAL

[0128] Anhydrous chloroform and toluene was obtained from Aldrich isdegassed by bubbling dry nitrogen gas throughout. Potassium hydroxidewas obtained from EM Science and powdered by mortar and pestle. Sodiumhydride was obtained as a 95% dry solid from Aldrich. IMesH₂Cl wasprepared according to a modified version of the procedure described inScholl et al. (1999) Org. Lett. 1:953-956 and Jafarpour et al. (2000)Organometallics 19:2055-2057. Unless otherwise specified, all otherreagents were purchased from commercial suppliers and used withoutfurther purification. All other solvents were purified by passagethrough a solvent column (containing activated A-2 alumina; see Pangbomet al. (1996) Organometallics 15:1518-1520.). Analytical thin-layerchromatography (TLC) was performed using silica gel 60 F254 precoatedplates (0.25 mm thickness) with a fluorescent indicator. Flash columnchromatography was performed using silica gel 60 (230-400 mesh) from EMScience. ¹H, ¹³C, and ³¹P NMR spectra were obtained on a Varian 300 MHzFourier Transform spectrometer (300 MHz ¹H, 75.4 MHz ¹³C, 121.4 MHz³¹P). All chemical shift values are given in parts-per million (δ) andare referenced with respect to residual solvent (¹H and ¹³C) orphosphoric acid (³¹P). In Examples 1-3, all operations were performedunder an inert atmosphere in a nitrogen-filled dry-box or by usingstandard Schlenk techniques.

[0129] Preparation of IMesH₂Cl: IMesH₂Cl, used as a starting material inExamples 1 through 3, was synthesized according to the following scheme:

[0130] To a solution of glyoxal (9 mL, 79 mmol, 40% wt in H₂O) inisopropanol (100 mL) and H₂O (200 mL) was added mesitylamine (25 mL, 2.2eq.) at 0° C. The reaction mixture was stirred while allowing to warm toroom temperature. Immediately upon addition of amine, yellowprecipitates were formed. After 24 hrs of stirring at ambienttemperature, the precipitates were filtered and washed with H₂O (1×100mL) and hexanes (3×100 mL). The yellow precipitates obtained were driedin vacuo to yield the diimine (20.6 g, 89%).

[0131] To a solution of diimine (8.0 g, 27.3 mmol) in THF (100 mL) wasadded NaBH4 (4.24 g, 112.1 mmol) at 0° C. Concentrated HCl (4.5 mL, 2eq.) was added dropwise over 30 minutes. After the HCl addition, thereaction mixture was stirred at 0° C. for 20 min. Then, 3 M HCl (250 mL)was added carefully to the flask at 0° C. and the mixture was stirredfor an additional 1 hr, allowing the temperature to rise to ambienttemperature. The resulting white precipitates were filtered and washedwith water (200 mL) and 5% acetone-ether (150 mL). The product (9.4 g,93%) was obtained as a white solid and dried in vacuo. To a suspensionof the HCl salt (8.5 g, 23 mmol) in HC(OEt)3 (35 mL, 162 mmol) was added2 drops of HCO₂H (adding about 1 mol%). The reaction mixture was thenheated at 120° C. for 5 hr under Ar. Then, the reaction mixture wascooled to an ambient temperature and hexane (200 mL) was added. Themixture was stirred for 1 hr and the white precipitates were filtered,washed with hexane (˜200 mL) and dried in vacuo to yield the IMesH₂HClsalt (7.6 g, 96%).

EXAMPLE 1 Representative Procedure for Synthesis of Ruthenium AlkylideneCatalysts from Substituted Alkynes

[0132] Synthesis of RuCl₂(═CH—CH═C(CH₃)₂)(IMesH₂)(PCy₃) (complex (2),Scheme 2):

[0133] [Ru(COD)Cl₂]_(n) (300 mg, 1 mmol), IMesH₂Cl (1.47 g, 4 mmol),tricyclohexylphosphine (300 mg, 1 mmol), and KN(SiMe₃)₂ (540 mg, 2.5mmol) were weighed directly into a 600 mL Schlenk tube. The flask wasevacuated and filled with dry argon (2×). Degassed benzene (300 mL) wasadded and the flask was pressurized to 30 psi with H₂. The suspensionwas vigorously stirred for 12 hours at 90° C., yielding a bright yellowsolution and white precipitate (1). After cooling the reaction to 5° C.,propargyl chloride (0.3 mL, 4 mmol) was slowly added via syringe and thereaction mixture was allowed to warm to room temperature. The resultingbrown benzene solution was washed with degassed 1 M HCl (2×), degassedbrine (2×), filtered through Celite and concentrated in vacuo to affordcompound (2) as a brown solid in 90% yield (˜95% purity). The brownsolid displayed catalytic behavior identical with previously synthesizedsecond-generation catalysts. Analytically pure (2) was obtained bycolumn chromatography on silica gel (degassed 3:1 hexanes/Et₂O). ¹H NMR(CD₂Cl₂): δ18.49 (d, J=11.1 Hz, 1H), 7.26 (d, J=10.9 Hz, 1H), 6.97 (s,2H), 6.77 (s, 2H), 3.92 (m, 4H), 2.58 (s, 6H), 2.37 (s, 6H), 2.29 (s,3H), 2.23 (s, 3H), 0.88-1.584 (m, 33H), 1.06 (s, 3H), 1.08 (s, 3H). ³¹PNMR (CD₂Cl₂): δ28.9. The reaction was repeated several times with one ormore reaction conditions modified so as to optimize the yield of theproduct. It was found that the yield could be increased to greater than95% by reducing the reaction temperature from 90° C. to 80° C.

[0134] Analogous ruthenium alkylidene complexes can be prepared usingthe aforementioned protocol and differently substituted phosphines,alkynes, etc., as indicated in the following two examples.

EXAMPLE 2 Scaled-Up Procedure for Synthesis of Complex (2) RutheniumAlkylidene Catalysts from Substituted Alkynes

[0135] After optimizing reaction conditions for the synthesis of Example1, i.e., to afford high yields of complex (2), a large scale (˜5 g)reaction was set up. A Schlenk flask containing a magnetic stir bar wascharged with [RuCl₂(COD)]_(n), IMesH₂Cl (4 equiv), and KN(SiMe₃)₂ (2.5equiv) and placed under an atmosphere of argon. A benzene solutioncontaining PCy₃ (1 equiv) was added via cannula and the flask waspressured with H₂ (30 psi). After stirring the reaction for 12 hours at80° C., the flask was cooled to 5° C. and propargyl chloride was addedvia syringe. An immediate color change from yellow to brown occurredindicating the conversion of (1) to (2). The solution was washed with 1MHCl (1×) and brine (2×) then concentrated to give complex (2) as a finetan powder in 90% yield.

EXAMPLE 3

[0136] Synthesis of RuCl₂(═CH—CH═C(CH₃)₂)(IMesH₂)(PPh₃) (Complex (4),Scheme 3):

[0137] The procedure of Example 1 was employed using [Ru(COD)Cl₂]_(n)(300 mg, 1 mmol), IMesH₂Cl (0.74 g, 2 mmol), triphenylphosphine (280 mg,1 mmol), and KN(SiMe₃)₂ (380 mg, 1.9 mmol), giving 550 mg (68%) ofcomplex (4). ³¹P NMR (CD₂Cl₂): δ24.0. ¹H NMR (CD₂Cl₂): δ18.49 (d, J=11.1Hz, 1H).

EXAMPLE 4

[0138] As may be deduced from Example 1, an excess of IMesH₂Cl is neededto optimize the yield of the product (decomposition of IMesH₂ wasdetermined to be competitive with formation of the hydride intermediateRuCl(H)(H₂)(IMesH₂)(PCy₃)(1). To circumvent the need for excessIMesH₂Cl, synthesis of the intermediate (1) was carried out with aruthenium complex that was pre-ligated with an imidazolylidene ligand,RuCl₂(IMesH₂)(p-cymene), as follows:

[0139] (a) Preparation of IMesH₂ chloroform adduct, IMesH₂—CCl₃(2-trichloromethyl-1,3-mesityl-4,5-dihydroimidazol-2-ylidene) (compound(5), Scheme 4):

[0140] IMesH₂Cl (10 g, 29 mmol) was dissolved in dry, degassedchloroform (250 mL) in a flame dried 1000 mL round-bottomed flaskequipped with stirbar. Sodium hydride (695 mg, 29 mmol) was then slowlyadded to the flask, and the resulting suspension was rapidly stirred atroom temperature for 90 minutes. It was then vacuum filtered to removeprecipitated sodium chloride, and concentrated in vacuo to a whitesolid. The product was further purified by recrystallization fromboiling hexanes to give a white crystalline solid (11.7 g, 94% yield).¹H NMR (CD₂Cl₂): δ6.877 (s, 2H), 6.854 (s, 2H), 5.595 (s, 1H), 3.92 (m,2H), 3.31 (m, 2H), 2.496 (s, 6H), 2.461 (s, 6H), 2.26 (s, 6H). ¹³C NMR(CD₂Cl₂): δ142.164 (s), 138.594 (s), 135.229 (s), 134.346 (s), 130.834(s), 130.546 (s), 109.468 (s), 86.503(s), 52.318 (s), 21.780 (s), 21.005(s), 20.268 (s).

[0141] Synthesis of RuCl₂(IMesH₂)(p-cymene) (Complex (6), Scheme 5):

[0142] [(p-cymene)RuCl₂]₂ (80 mg, 0.13 mmol) and chloroform adduct (5)formed in (a) (140 mg, 0.3 mmol) were weighed into a round bottom flaskequipped with a magnetic stir bar and reflux condenser. Ahexanes:benzene mixture (10:1, 4 mL) was added and the reaction wasplaced under an argon atmosphere. After 4 hours of reflux, the reactionwas cooled to room temperature and the tan precipitate was collected,washed with copious amounts of hexanes and dried in vacuo to afford thedesired product (6) quantitatively. ¹H NMR (C₆D₆): δ6.523 (s, 4H), 5.254(d, 2H), 4.882 (d, 2H), 3.948 (bs, 4H), 3.288 (m, 1H), 2.105 (s, 3H),2.072 (s, 12H), 2.011 (s, 6H), 1.268 (d, 6H).

EXAMPLE 5

[0143] Synthesis of (PCy₃)(IMesH₂)Cl₂Ru═C═C(CH₃)₃ (complex (7), Scheme6):

[0144] The p-cymene complex prepared in Example 4(b) can also be useddirectly, without isolation or purification, in the synthesis of metalvinylidene complexes. The following describes such a method, whereinRuCl₂(IMesH₂)(p-cymene) (6) is converted to the vinylidene complex(PCy₃)(IMesH₂)Cl₂Ru═C═C(CH₃)₃ (7), as illustrated in Scheme 5:RuCl₂(IMesH₂)(p-cymene), prepared in Example 4 (10 mg, 0.016 mmol), PCy₃(5 mg, 0.016 mmol), and t-butyl acetylene (2 μL, 0.016 mmol) weredissolved in 0.6 mL C₆D₆ and transferred to a screw top NMR tube. Thereaction was heated to 80° C. for 8 hours to afford (7).

EXAMPLE 6 Synthesis of Chloroform Adducts With Potassium Hydroxide

[0145] General Procedures. Potassium hydroxide was powdered with amortar and pestle immediately prior to use. Anhydrous chloroform wasused as obtained from Aldrich Chemical Company. Deuterated solvents wereused as obtained from Cambridge Scientific. NMR spectra were recorded onOxford Instruments 300 MHz NMR spectrometers running Varian VNMRsoftware.

[0146] General procedure for NMR screening. Powdered potassium hydroxide(20 mg) was added to a screw-cap 10 dram vial equipped with stirbar.Deuterated benzene (0.7 mL) was added to the solid via syringe, forminga thick suspension. Chloroform (10 μL, 129 μmol, 3 eq.) was then addedto the rapidly stirred suspension at room temperature. After 15 minutes,the imidazolium salt (either chloride or tetrafluoroborate counterion,43 μmol, 1 eq.) was added to the suspension as a solid. After 30-45minutes, the supernatant was decanted into a screw-cap NMR tube and the¹H NMR spectrum was recorded. In each case the ipso proton(N—C(H)(CCl₃)—N) was cleanly observed in the range of 5.0-5.8 ppm.

[0147] Representative procedure for chloroform adduct formation (Table1): Dry, degassed toluene (8.2 mL) was added to a flame dried 50 m Lround-bottomed flask equipped with stirbar and reflux condenser. A largeexcess of potassium hydroxide (>10 mmol) was added to the flask, and theresulting suspension was rapidly stirred at room temperature. Chloroform(77 μL, 0.96 mmol) was added to this suspension via microsyringe. After10 minutes, IMesH₂Cl (100 mg, 0.29 mmol) was added, and the reactionmixture was then heated to 60° C. for 75 minutes. The mixture wasallowed to cool to room temperature, vacuum filtered, and concentratedin vacuo to a yellowish-white solid. This crude product was thenpurified by filtration through a silica gel plug, eluting with 9:1hexanes:ethyl acetate. The product was further purified byrecrystallization from boiling hexanes to give a white solid (110 mg,88% yield). The reaction was repeated with one or more differentreaction parameters (e.g., base, solvent, temperature, time), withresults indicated in Table 1.

EXAMPLE 7 Preparation of Ruthenium Alkylidene Catalysts

[0148] Preparation of ruthenium alkylidene catalysts coordinated withimidazolylidenes derived from the chloroform adducts synthesized inExample 6 (Table 2). To a solution of chloroform adduct (approximately21 μmol) in deuterated benzene (0.7 mL) was addedbis-(tricyclohexylphosphine)dichlororuthenium (II) benzylidene (9 mg, 11μmol) as a solid. Periodic ¹H NMR spectra were recorded at 10 degreeintervals between room temperature and 80° C. Formation of new complexeswas observed in the 18-22 ppm region of the ¹H NMR spectra.

We claim:
 1. A method for synthesizing a transition metal carbenecomplex having the structure of formula (V)

M is a Group 8 transition metal, X¹and X² may be the same or different,and are anionic ligands or polymers; R, R¹ and R² are independentlyselected from the group consisting of hydrogen, hydrocarbyl, substitutedhydrocarbyl, heteroatom-containing hydrocarbyl, substitutedheteroatom-containing hydrocarbyl, and -(Z)_(n)-Fn where n is zero or 1,Z is a hydrocarbylene, substituted hydrocarbylene and/orheteroatom-containing hydrocarbylene linkage, and Fn is a functionalgroup; L is any neutral electron donor ligand; L¹ is a neutral electrondonor ligand having the structure of formula (VI)

X and Y are heteroatoms selected from N, O, S, and P, p is zero when Xis O or S, and is 1 when X is N or P, q is zero when Y is O or S, and is1 when Y is N or P, Q¹, Q², Q³, and Q⁴ are selected from hydrocarbylene,substituted hydrocarbylene, heteroatom-containing hydrocarbylene,substituted heteroatom-containing hydrocarbylene, and —(CO)—; w, x, yand z are independently zero or 1; and R³, R^(3A), R⁴, and R^(4A) areindependently selected from the group consisting of hydrogen,hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl,and substituted heteroatom-containing hydrocarbyl, wherein any two ormore of X¹, X², L, R, R¹, and R² can be taken together to form achelating multidentate ligand, the method comprising: (a) combining (i)a metal complex ML³(XI)₂, where M and X¹ are as defined above and L³ isa bidentate organic ligand, with (ii) a salt or adduct of L¹, (iii) anucleophilic base; and (c) L, in (d) the presence of hydrogen gas, underconditions effective to provide the dihydrogen complex (VII)

(b) contacting the dihydrogen complex (VII) with an alkyne of theformula (VIII)

wherein R, R¹, R² and X² are as defined previously.
 2. The method ofclaim 1, wherein M is Ru or Os.
 3. The method of claim 2, wherein thesalt or adduct of L¹ is selected from a halide salt and atrichloromethyl adduct.
 4. The method of claim 2, wherein thenucleophilic base is a nitrogenous base containing at least onesubstituent selected from secondary alkyl, tertiary alkyl, cycloalkyl,aryl, and tri(alkyl)silyl groups.
 5. The method of claim 4, wherein thenucleophilic base is of the formula M¹N(SiR¹⁵ ₃)₂ in which M¹ is analkali metal and R¹⁵ is alkyl.
 6. The method of claim 5, wherein thenucleophilic base is KN[Si(CH₃)₃]₂.
 7. The method of claim 2, whereinstep (a) is carried out in a substantially nonpolar solvent at atemperature in the range of approximately 55° C. to approximately 90° C.8. The method of claim 2, wherein L is a neutral electron donor ligandselected from the group consisting of phosphine, sulfonated phosphine,phosphite, phosphinite, phosphonite, arsine, stibine, ether, amine,amide, imine, sulfoxide, carboxyl, nitrosyl, pyridine, substitutedpyridine, imidazole, substituted imidazole, pyrazine, and thioether. 9.The method of claim 8, wherein L is a phosphine of the formula PR⁵R⁶R⁷,where R⁵, R⁶, and R⁷ are each independently aryl or C₁-C₁₀ alkyl. 10.The method of claim 9, wherein L is selected from the group consistingof tricyclohexylphosphine, tricyclopentylphosphine,triisopropylphosphine, triphenylphosphine, diphenylmethylphosphine, andphenyldimethylphosphine.
 11. The method of claim 2, wherein L³ is1,5-cyclooctadiene.
 12. The method of claim 2, wherein w, x, y and z arezero, X and Y are N, and R^(3A)and R^(4A) are linked to form —Q—, suchthat L¹ has the structure of formula (IX)

wherein Q is a hydrocarbylene, substituted hydrocarbylene,heteroatom-containing hydrocarbylene, or substitutedheteroatom-containing hydrocarbylene linker, and further wherein two ormore substituents on adjacent atoms within Q may be linked to form anadditional cyclic group.
 13. The method of claim 12, wherein Q has thestructure —CR⁸R^(8A)—CR⁹R^(9A) or —CR⁸═CR⁹—, wherein R⁸, R^(8A), R⁹, andR^(9A) are substituents independently selected from the group consistingof hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containinghydrocarbyl, substituted heteroatom-containing hydrocarbyl, and-(Z)_(n)-Fn where n is zero or 1, Z is alkylene or substituted alkylene,and Fn is phosphonato, phosphoryl, phosphanyl, phosphino, sulfonato,C₁-C₂₀ alkylsulfanyl, C₅-C₂₀ arylsulfanyl, C₁-C₂₀ alkylsulfonyl, C₅-C₂₀arylsulfonyl, C₁-C₂₀ alkylsulfinyl, C₅-C₂₀ arylsulfinyl, sulfonamido,amino, amido, imino, nitro, nitroso, hydroxyl, C₁-C₂₀ alkoxy, C₅-C₂₀aryloxy, C₂-C₂₀ alkoxycarbonyl, C₅-C₂₀ aryloxycarbonyl, carboxyl,carboxylato, mercapto, formyl, C₁-C₂₀ thioester, cyano, cyanato,carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl, siloxazanyl,boronato, boryl, halogen, stannyl, or germyl, any of which, if thesubstituent permits, may be further substituted with additionalhydrocarbyl and/or -(Z)_(n)-Fn moieties, and further wherein any two ormore of R³, R⁴, R⁸, R^(8A), R⁹, and R^(9A) are optionally linked to forma cyclic group.
 14. The method of claim 13, wherein Q has the structure—CR⁸R^(8A)—CR⁹R^(9A)—.
 15. The method of claim 14, wherein: X¹ and X²are independently selected from the group consisting of hydrogen,halide, C₁-C₂₀ alkyl, C₅-C₂₀ aryl, C₁-C₂₀ alkoxy, C₅-C₂₀ aryloxy, C₃-C₂₀alkyldiketonate, C₅-C₂₀ aryldiketonate, C₂-C₂₀ alkoxycarbonyl, C₁-C₂₀aryloxycarbonyl, C₂-C₂₀ acyl, C₁-C₂₀ alkylsulfonato, C₅-C₂₀arylsulfonato, C₁-C₂₀ alkylsulfanyl, C₅-C₂₀ arylsulfanyl, C₁-C₂₀alkylsulfinyl, or C₅-C₂₀ arylsulfinyl, any of which, with the exceptionof hydrogen and halide, are optionally further substituted with one ormore groups selected from halide, C₁-C₆ alkyl, C₁-C₆ alkoxy, and phenyl;R is hydrogen and R¹ and R² are selected from the group consisting ofhydrogen, C₁-C₂₀ alkyl, C₅-C₂₀ aryl, and -(Z)_(n)-Fn where Z is alkyleneor substituted alkylene, and Fn is phosphonato, phosphoryl, phosphanyl,phosphino, sulfonato, C₁-C₂₀ alkylsulfanyl, C₅-C₂₀ arylsulfanyl, C₁-C₂₀alkylsulfonyl, C₅-C₂₀ arylsulfonyl, C₁-C₂₀ alkylsulfinyl, C₅-C₂₀arylsulfinyl, sulfonamido, amino, amido, imino, nitro, nitroso,hydroxyl, C₁-C₂₀ alkoxy, C₅-C₂₀ aryloxy, C₂-C₂₀ alkoxycarbonyl, C₅-C₂₀aryloxycarbonyl, carboxyl, carboxylato, mercapto, formyl, C₁-C₂₀thioester, cyano, cyanato, carbamoyl, epoxy, styrenyl, silyl, silyloxy,silanyl, siloxazanyl, boronato, boryl, halogen, stannyl, or germyl; R³and R⁴ are aromatic, substituted aromatic, heteroaromatic, substitutedheteroaromatic, alicyclic, substituted alicyclic, heteroatom-containingalicyclic, or substituted heteroatom-containing alicyclic, composed offrom one to about five rings; and R⁸ and R⁹ are hydrogen, and R^(8A) andR^(9A) are selected from hydrogen, lower alkyl and phenyl, or are linkedto form a cyclic group.
 16. The method of claim 15, wherein: X¹and X²are independently selected from the group consisting of halide, CF₃CO₂,CH₃CO₂, CFH₂CO₂, (CH₃)₃CO, (CF₃)₂(CH₃)CO, (CF₃)(CH₃)₂CO, PhO, MeO, EtO,tosylate, mesylate, and trifluoromethanesulfonate; R¹ and R² areselected from the group consisting of hydrogen, C₁-C₆ alkyl, and C₅-C₂₀aryl; and R³ and R⁴ are the same and are either aromatic or C₇-C₁₂alicyclic, if aromatic, each having the structure (X)

in which R¹⁰, R¹¹, and R¹² are each independently hydrogen, C₁-C₂₀alkyl, substituted C₁-C₂₀ alkyl, C₁-C₂₀ heteroalkyl, substituted C₁-C₂₀heteroalkyl, C₅-C₂₀ aryl, substituted C₅-C₂₀ aryl, C₅-C₂₀ heteroaryl,C₅-C₃₀ aralkyl, C₅-C₃₀ alkaryl, or halogen.
 17. The method of claim 16,wherein: X¹ and X² are halide; R¹ and R² are methyl; R³ and R⁴ aremesityl; L is selected from the group consisting of —P(cyclohexyl)₃ and—P(cyclopentyl)₃; and R^(8A) and R^(9A) are hydrogen.
 18. A method forsynthesizing a ligand precursor having the structure of formula (XI)

in which R³, R⁴, R⁸, R^(8A), R⁹, and R^(9A) are substituentsindependently selected from the group consisting of hydrogen,hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl,substituted heteroatom-containing hydrocarbyl, and -(Z)_(n)-Fn where nis zero or 1, Z is Z is hydrocarbylene, substituted hydrocarbyleneand/or heteroatom-containing hydrocarbylene, and Fn is phosphonato,phosphoryl, phosphanyl, phosphino, sulfonato, C₁-C₂₀ alkylsulfanyl,C₅-C₂₀ arylsulfanyl, C₁-C₂₀ alkylsulfonyl, C₅-C₂₀ arylsulfonyl, C₁-C₂₀alkylsulfinyl, C₅-C₂₀ arylsulfinyl, sulfonamido, amino, amido, imino,nitro, nitroso, hydroxyl, C₁-C₂₀ alkoxy, C₅-C₂₀ aryloxy, C₂-C₂₀alkoxycarbonyl, C₅-C₂₀ aryloxycarbonyl, carboxyl, carboxylato, mercapto,formyl, C₁-C₂₀ thioester, cyano, cyanato, carbamoyl, epoxy, styrenyl,silyl, silyloxy, silanyl, siloxazanyl, boronato, boryl, halogen,stannyl, or germyl, any of which, if the substituent permits, may befurther substituted with additional hydrocarbyl and/or -(Z)_(n)-Fnmoieties, and further wherein any two or more of R³, R⁴, R⁸, R^(8A), R⁹,and R^(9A) are optionally linked to form a cyclic group, wherein themethod comprises: contacting a compound having the structure of formula(XII)

with chloroform and a non-nucleophilic base effective to deprotonate thechloroform, wherein, in formula (XII), X⁻ is an anionic counterion. 19.The method of claim 18, wherein the non-nucleophilic base is aninorganic hydroxide, a metal hydride, or an organolithium reagent. 20.The method of claim 19, wherein the non-nucleophilic base is an alkalimetal hydroxide.
 21. The method of claim 19, wherein thenon-nucleophilic base is sodium hydride.
 22. The method of claim 18,wherein X⁻ is a halide ion.
 23. A method for synthesizing a transitionmetal carbene complex from the bisphosphine complex(XI)(X²)(PR⁵R⁶R⁷)₂M═CRR¹⁴ wherein M is Ru or Os, X¹ and X² are anionicligands, R⁵, R⁶, and R⁷ are each independently aryl or C₁-C₁₀ alkyl, andR and R¹⁴ are independently selected from the group consisting ofhydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containinghydrocarbyl, substituted heteroatom-containing hydrocarbyl, and-(Z)_(n)-Fn where n is zero or 1, Z is hydrocarbylene, substitutedhydrocarbylene and/or heteroatom-containing hydrocarbylene, and Fn is afunctional group, wherein the method comprises: contacting thebisphosphine complex with a ligand precursor having the formula

in which R³, R⁴, R⁸, R^(8A), R⁹, and R^(9A) are substituentsindependently selected from the group consisting of hydrogen,hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl,substituted heteroatom-containing hydrocarbyl, and -(Z)_(n)-Fn, therebyproviding the transition metal carbene complex (XIII)


24. The method of claim 23, wherein: M is Ru; X¹ and x² areindependently selected from the group consisting of hydrogen, halide,C₁-C₂₀ alkyl, C₅-C₂₀ aryl, C₁-C₂₀ alkoxy, C₅-C₂₀ aryloxy, C₃-C₂₀alkyldiketonate, C₅-C₂₀ aryldiketonate, C₂-C₂₀ alkoxycarbonyl, C₅-C₂₀aryloxycarbonyl, C₂-C₂₀ acyl, C₁-C₂₀ alkylsulfonato, C₅-C₂₀arylsulfonato, C₁-C₂₀ alkylsulfanyl, C₅-C₂₀ arylsulfanyl, C₁-C₂₀alkylsulfinyl, or C₅-C₂₀ arylsulfinyl, any of which, with the exceptionof hydrogen and halide are optionally further substituted with one ormore groups selected from halide, C₁-C₆ alkyl, C₁-C₆ alkoxy, and phenyl;R is hydrogen; R¹⁴ ⁴ is selected from the group consisting of hydrogen,C₁-C₂₀ alkyl, C₅-C₂₀ aryl; R³ and R⁴ are aromatic, substituted aromatic,heteroaromatic, substituted heteroaromatic, alicyclic, substitutedalicyclic, heteroatom-containing alicyclic, or substitutedheteroatom-containing alicyclic, composed of from one to about fiverings; and R⁸ and R⁹ are hydrogen, and R^(8A) and R^(9A) are selectedfrom hydrogen, lower alkyl and phenyl, or are linked to form a cyclicgroup.
 25. The method of claim 24, wherein the bisphosphine complex is(phenylmethylene-bis(tricyclohexylphosphine) ruthenium dichloride andthe ligand precursor is 2-trichloromethyl-4,5-dihydroimidazolidine. 26.A method for synthesizing a transition metal alkylidene complex offormula (XIV)

wherein M is Ru or Os, X¹ and X² are anionic ligands, L is P(R⁵R⁶R⁷),R⁵, R⁶, and R⁷ are each independently aryl or C₁-C₁₀ alkyl, R, R¹ and R²are independently selected from the group consisting of hydrogen,hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl,substituted heteroatom-containing hydrocarbyl, and -(Z)_(n)-Fn where nis zero or 1, Z is a hydrocarbylene linkage, and Fn is a functionalgroup, and R³, R⁴, R⁸, R^(8A), R⁹, and R^(9A) are substituentsindependently selected from the group consisting of hydrogen,hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl,substituted heteroatom-containing hydrocarbyl, and -(Z)_(n)-Fn, whereinthe method comprises: (a) contacting the ligand precursor (XI)

with M(XI)₂(L⁴)₂, wherein L⁴ is an eta-6 coordinating ligand, to providethe intermediate (XV)

(b) contacting intermediate (XV) with P(R⁵R⁶R⁷) in the presence ofhydrogen and a base, to give the dihydrogen complex (XVI)

(d) thereafter treating the dihydrogen complex (XVI) with an alkyne ofthe formula (VIII)

wherein R, R¹, R² and X² are as defined previously.
 27. A method forsynthesizing a transition metal vinylidene complex of formula (XVII)

wherein M is Ru or Os, X¹ and X² are anionic ligands, R¹³ is selectedfrom the group consisting of hydrogen, hydrocarbyl, substitutedhydrocarbyl, heteroatom-containing hydrocarbyl, substitutedheteroatom-containing hydrocarbyl, and -(Z)_(n)-Fn where n is zero or 1,Z is a hydrocarbylene linkage, and Fn is a functional group, and R³, R⁴,R⁸, R^(8A), R⁹, and R^(9A) are substituents independently selected fromthe group consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl,heteroatom-containing hydrocarbyl, substituted heteroatom-containinghydrocarbyl, and -(Z)_(n)-Fn, wherein the method comprises: (a)contacting the ligand precursor (XI)

with MX¹X²(L⁴)₂, wherein L⁴ is an eta-6 coordinating ligand, to providethe intermediate (XV)

thereafter treating intermediate (XIV) with an alkyne of the formulaH—C≡C—R¹³.